Salk Study: Delaying Aging Delays Alzheimers, In Mice

SAN DIEGO ---- The onset of Alzheimer's disease can be delayed
---- in mice ---- a discovery with strong implications for
improving the healthy part of human lifespans, according to
research by Salk Institute scientists.

The research also supports a relatively new theory that the
plaques of toxic proteins found in brain cells of Alzheimer's
patients are not the cause of the disease. Instead, the clumps are
made by cells stowing away the toxic beta amyloid proteins where
they can't do damage, said Andrew Dillin, a Salk professor who led
the study.

Researchers used mice given human genes to overproduce beta
amyloid, causing Alzheimers-like symptoms. Some of these mice were
genetically modified again to prolong their life, by reducing the
activity of a genetic system, or "pathway," called IGF-1, which is
also found in fruitflies and nematode worms as well as humans. The
pathway, known to affect the aging process, was altered to lower
its activity.

The mice with the lowered IGF-1 function not only lived 35
percent longer, but the onset of mental decline was also delayed.
This protection against a classic disease of aging is evidence that
treatment in humans would likewise increase our span of healthy
life, or "healthspan," Dillin said.

Human treatment would be with a drug to lower the pathway's
function, Dillin said, and it's reasonable to expect that human
clinical trials could begin in about five to 10 years.

"We know in exquisite detail about this pathway, and all the
molecular players in it," Dillin said. "So we know how to drug that
pathway."

The same mutation is also found naturally in some human
centenarians, who are known for being lucid-minded, Dillin
said.

The study was released Thursday, and will be published in
Friday's issue of the scientific journal Cell.

One of the surprises in genetic research over the last few
decades is just how closely related animals are in their basic
genetic functions, even those as distantly related to humans as
fruit flies and nematode worms.

While nematodes are not known for losing their car keys or
otherwise displaying memory impairment, Dillin said the cells of
what passes for a brain in them show signs of degeneration. The
experiments in mice, much more closely related to humans, give
reason to hope the therapy could work in humans.

The Alzheimer's-prone mice were tested for memory loss in
crossing a maze that had a submerged underwater platform. The
treated mice retained their ability longer. Their brains still
showed beta amyloid plaques, but the plaques were fewer and larger
than plaques in untreated mice, and took up less area in the
brain.

Dillin and his cohorts are testing the theory for other diseases
in mice, to see if the same protective effect applies.

"Right now, we're testing Parkinson's disease, Huntington's
disease, Lou Gehrig's disease ... many of the age-onset
neurodegenerative diseases will be a target of this. We think it
will be protective for all of those."

A question the study raises is why the mutant IGF-1 gene with
lowered function more common. Dillin said the mutant gene also
imposes disadvantages: The treated mice are smaller and less
fertile than untreated mice. So there is an evolutionary pressure
working against the gene spreading.

But this doesn't have to apply to humans, Dillin said. This
effect could be sidestepped by beginning the drug therapy after
people have grown up, perhaps in their 50s, he said.

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My original article is below:

LA JOLLA ---- The onset of Alzheimer's disease can be delayed --
in mice -- with strong implications for improving the healthy part
of human lifespans, according to research by Salk Institute
scientists.

The genetically modified mice not only lived 35 percent longer,
but the onset of mental decline was also delayed, This protection
against a classic disease of aging is evidence that treatment in
humans would likewise increase our span of healthy life, or
"healthspan," said
Andrew Dillin
, a Salk
professor who led the study.

Treatment would be with a drug, Dillin said, and it's reasonable
to expect that human clinical trials could begin in about five to
10 years, Dillin said.

The research also supports a relatively new theory that the
plaques of toxic proteins found in brain cells of Alzheimer's
patients are not the cause of the disease. Instead, the clumps of
beta amyloid proteins are how cells stow away the toxic proteins
where they can't do damage, Dillin said.

The study will be published in the Dec. 11 issue of Cell.

Researchers used mice that develop Alzheimer's-like symptoms.
These mice were genetically modified to prolong their life, using a
genetic system, or "pathway" called IGF-1, also found in fruitflies
and C. elegans nematodes, as well as humans. The pathway was
altered to lower its activity.

"We know in exquisite detail about this pathway, and all the
molecular players in it," Dillin said. "So we know how to drug that
pathway."

The same mutation is also found naturally in some human
centenarians, who are known for being lucid-minded, Dillin
said.

While nematode worms are not known for losing their car keys or
otherwise displaying memory loss, Dillin said the cells of what
passes for a brain in them show signs of degeneration.

The Alzheimer's mouse model was tested for memory loss in
crossing a maze that had a submerged underwater platform. The
treated mice retained their ability longer. Their brains still
showed beta amyloid plaques, but the plaques were fewer and larger
than plaques in untreated mice, and took up less area in the
brain.

Dillin and his cohorts are testing the theory on mice models of
other diseases, to see if the same protective effect applies.

The treated mice are smaller and less fertile than untreated
mice, Dillin said. This effect could be sidestepped by beginning
the drug therapy after people have grown up, perhaps in their 50s,
he said.